Assessment of the Effect of Empagliflozin (BI 10773) as Single Dose on the QT Interval in Healthy Female and Male Subjects

Mean QTcN (heart rate-corrected QT interval, using a study population-based approach) from the ECGs obtained between 1h to 4h following drug administration minus the mean QTcN from the baseline ECGs obtained pre-dose at each visit, for empa 200mg. Note, the treatment means presented are actually adjusted means.

Time frame: 60 minutes (min), 50min and 40 min before the first dose and 1 hour (h), 1.5h, 2h, 2.5h, 3h and 4h after the first dose

Population: Full analysis set (FAS): all treated subjects who had at least one baseline assessment and at least one post-baseline assessment for at least one ECG endpoint.

Mean QTcN (heart rate-corrected QT interval, using a study population-based approach) from the ECGs obtained between 1h to 4h following drug administration minus the mean QTcN from the baseline electrocardiogram (ECGs) obtained pre-dose at each visit, for empa 25mg. Note, the treatment means presented are actually adjusted means.

Time frame: 60 minutes (min), 50min and 40 min before the first dose and 1 hour (h), 1.5h, 2h, 2.5h, 3h and 4h after the first dose

Population: Full analysis set (FAS): all treated subjects who had at least one baseline assessment and at least one post-baseline assessment for at least one ECG endpoint.

Change from mean baseline in QTcN at each time point between 30 minutes and 24 hours after dosings for empa 200mg. The clinically relevant information (and endpoint resulting from ICH E14) is shown by the maximum upper confidence limit value over time. For this outcome results are presented for the 2.5 hour timepoint as this was when the maximum value was seen. Note, the presented means are actually adjusted means.

Time frame: 60 minutes (min), 50min and 40 min before the first dose and 0.5 hour (h), 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h and 24h after the first dose

Population: Full analysis set (FAS): all treated subjects who had at least one baseline assessment and at least one post-baseline assessment for at least one ECG endpoint.

Mean changes from baseline in QTcN from all ECGs taken between 30 minutes and 24 hours after dosings, for empa 200 mg. Note, presented means are actually adjusted means.

Time frame: 60 minutes (min), 50min and 40 min before the first dose and 30min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h and 24h after the first dose

Population: Full analysis set (FAS): all treated subjects who had at least one baseline assessment and at least one post-baseline assessment for at least one ECG endpoint.

Change from mean baseline in QTcN at each time point between 30 minutes and 24 hours after dosings for empa 25mg. The clinically relevant information (and endpoint resulting from ICH E14) is shown by the maximum upper confidence limit value over time. For this outcome results are presented for the 24 hour timepoint as this was when the maximum value was seen. Note, the presented means are actually adjusted means.

Time frame: 60 minutes (min), 50min and 40 min before the first dose and 0.5 hour (h), 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h and 24h after the first dose

Population: Full analysis set (FAS): all treated subjects who had at least one baseline assessment and at least one post-baseline assessment for at least one ECG endpoint.

Mean changes from baseline in QTcN from all ECGs taken between 30 minutes and 24 hours after dosings, for empa 25 mg. Note, presented means are actually adjusted means.

Time frame: 60 minutes (min), 50min and 40 min before the first dose and 30min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h and 24h after the first dose

Population: Full analysis set (FAS): all treated subjects who had at least one baseline assessment and at least one post-baseline assessment for at least one ECG endpoint.

Mean changes from baseline in QTcN from all ECGs taken between 2 hours and 4 hours after dosings Note, the means presented are actually adjusted means.

Time frame: 60 minutes (min), 50min and 40 min before the first dose and 2 hour (h), 2.5h, 3h and 4h after the first dose

Population: Full analysis set (FAS): all treated subjects who had at least one baseline assessment and at least one post-baseline assessment for at least one ECG endpoint.

Clinically relevant abnormalities for physical examination, vital signs, ECG, blood chemistry, haematology, urinanalysis and assessment of tolerability by the investigator. New abnormal findings or worsening of baseline conditions were reported as adverse events (AEs). Time frame for AE reporting includes the period of first drug administration until end of study. A more detailed definition of the used time frame and MedDRA Version can be found in the AE section.

Time frame: Drug administration until beginning of next sequence/end of trial, up to 48 days

Population: Treated set (TS): All subjects who were dispensed trial medication and were documented to have taken at least one dose of investigational treatment.

The placebo corrected change from mean baseline is defined per time point as the difference of the change from baseline for empa or moxifloxacin minus the average change from baseline obtained for the two administrations of placebo. The clinically relevant information (and endpoint resulting from ICH E14) is shown by the maximum mean value of all measurements. Results are presented for the greatest change, for empa 25mg the greatest change was seen at the 24 hour time point, for empa 200 mg and moxifloxacin the greatest change was seen at the 2.5 hour time point.

Time frame: 60 minutes (min), 50min and 40 min before the first dose and 30min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h and 24h after the first dose

Population: Full analysis set (FAS): all treated subjects who had at least one baseline assessment and at least one post-baseline assessment for at least one ECG endpoint.

The time-matched change from placebo is defined per time point as the difference of the ECG measurement following administration of empa or moxifloxacin minus the average of the measurements obtained following the two administrations of placebo. The clinically relevant information (and endpoint resulting from ICH E14) is shown by the maximum mean value of all measurements. Results are presented for the greatest change, for empa 25mg the greatest change was seen at the 24 hour time point, for empa 200 mg and moxifloxacin the greatest change was seen at the 2.5 hour time point.

Time frame: 60 minutes (min), 50min and 40 min before the first dose and 30min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h and 24h after the first dose

Population: Full analysis set (FAS): all treated subjects who had at least one baseline assessment and at least one post-baseline assessment for at least one ECG endpoint.